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首页> 外文期刊>Journal of Cellular Physiology >Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis
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Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis

机译:白藜芦醇抑制致瘤性和提高辐射敏感度原发性胶质母细胞瘤肿瘤启动细胞通过抑制STAT3轴

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Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133 + TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133 + in vitro and in vivo. Furthermore, treatment of GBM-CD133 + with 100μM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133 + and facilitated the differentiation of GBM-CD133 + into GBM-CD133 - or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway.
机译:多形性胶质母细胞瘤(GBM)是最常见的和积极的原发性脑瘤。诊断为“绿带运动”有一个预后不良,据报道,肿瘤恶性肿瘤和“绿带运动”复发被STAT3信号提升。白藜芦醇(RV),葡萄多酚,据报道一个强有力的和无毒的预防癌症的化合物,本研究的目的探讨治疗效果和分子机制GBM-derived房车抗放射性的肿瘤启动细胞(TIC)。首先,我们的研究结果表明,初选GBM-CD133 +抽搐高致瘤的和radiochemoresistant属性以及增加磷酸化STAT3的蛋白质含量。我们一直观察到治疗shRNA-STAT3 (sh-STAT3)前AG490, STAT3抑制剂,显著抑制癌症干细胞样细胞的特性和抗辐射性GBM-CD133 +体外和体内。治疗GBM-CD133 + 100μM房车诱导细胞凋亡和增强辐射敏感度抑制STAT3信号。建议房车或AG490抑制具备干细胞基因签名GBM-CD133 +和促进GBM-CD133 +成GBM-CD133的分化——或星形细胞瘤细胞。实验表明,房车或sh-STAT3疗法可以显著提高生存率和加强辐射敏感度的增效剂接受过放疗GBM-TIC。减少体内致瘤性和提高GBM-TIC放疗的敏感性STAT3通路。

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